TY - BOOK AU - Umans, Jason G TI - Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure SN - 0340-5761 PY - 2014/// KW - *Arsenic/to [Toxicity] KW - *Arsenic/ur [Urine] KW - *DNA Methylation/de [Drug Effects] KW - *Methyltransferases/ge [Genetics] KW - *Promoter Regions, Genetic/de [Drug Effects] KW - Aged KW - Cohort Studies KW - CpG Islands KW - Female KW - Gene Expression Regulation/de [Drug Effects] KW - Humans KW - Leukocytes, Mononuclear/de [Drug Effects] KW - Male KW - Methyltransferases/me [Metabolism] KW - Middle Aged KW - MedStar Health Research Institute KW - Journal Article KW - Research Support, N.I.H., Extramural N2 - Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase (AS3MT). Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena, including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for AS3MT, is differentially methylated as a function of arsenic exposure. In this study, we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989 to 1991 and 1998-1999. For this study, all data are from the 1989-1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation, and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene UR - http://dx.doi.org/10.1007/s00204-013-1146-x ER -